Biguanides have been used in the treatment of T2DM since the1950s. Derived from the French lilac, Galega officinalis, phenformin was the initial biguanide available for clinical use. It was taken off the market in the 1970s after numerous cases of lactic acidosis were found to be associated with its use. The etiology of the lactic acidosis was related to impaired hydroxylation of phenformin in a subset of individuals. In contrast, individuals taking metformin are at very low risk of developing this complication. Over time, metformin has proven to be safe and remains the only biguanide approved by the FDA for use in the USA.

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